Combination therapy for the treatment of autoimmune diseases

Abstract

The present invention pertains to compounds and their combination for use in the prevention or therapy of a subject suffering from an autoimmune disease such as diabetes type 1. Provided are antagonists of T-cells that are used in combination with antagonists of the cytokine CXCL10, sequentially or concomitantly, in a subject suffering from an autoimmune disease, in particular diabetes type 1.

Description

CROSS REFERENCE TO A RELATED APPLICATION[0001]This application is a continuation application of co-pending application Ser. No. 15 / 301,130, filed Sep. 30, 2016; which is a National Stage Application of International Application Number PCT / EP2014 / 057077, filed Apr. 8, 2014; all of which are incorporated herein by reference in their entirety.FIELD OF THE INVENTION[0002]The present invention pertains to compounds and their combination for use in the prevention or therapy of a subject suffering from an autoimmune disease such as diabetes type 1. Provided are antagonists of T-cells that are used in combination with antagonists of the cytokine CXCL10, sequentially or concomitantly, in a subject suffering from an autoimmune disease, in particular diabetes type 1.BACKGROUND OF THE INVENTION[0003]Diabetes type 1 is a serious autoimmune disorder resulting in the destruction of insulin producing beta cells of the Langerhans islets in the pancreas by the immune system. Without the constant supp...

AI Technical Summary

Benefits of technology

The patent describes a new therapy for autoimmune diseases, specifically diabetes type 1, that combines two different treatments. The first treatment targets T-cells, which are a type of immune cell that can attack and destroy beta cells in the pancreas, which produce insulin. The second treatment targets a chemokine called C-X-C motif chemokine 10 (CXCL10), which helps direct the movement of these T-cells. By using both treatments together, the therapy is more effective and can better prevent the destruction of beta cells and long-term suppression of diabetes type 1.

Problems solved by technology

In absence of insulin-supplementation patients will eventually die from the toxic blood glucose levels.

Destruction progresses subclinically over months or years until beta-cell mass decreases to the point that insulin concentrations are no longer adequate to control plasma glucose levels.

Even under constant insulin supplementation, treated patients develop long term damages such as severe disorders of the blood circulation and blindness.

Examples include the administration of Cyclosporine A, an immunosuppressive agent, that has apparently halted destruction of beta cells, but its nephrotoxicity and other side effects make it highly inappropriate for long-term use.

However, in 2011, Phase III studies with otelixizumab and teplizumab both failed to show clinical efficacy, potentially due to an insufficient dosing schedule.

Generally, the administration of CD3 antibodies might only delay disease progression but not prevent beta cell destruction on the long term (Keymeulen B et al., N Engl J Med 2005).

Such therapies are experienced as unpleasant by the patients and interfere with everyday life.

Disadvantage of this method is that it is rather inefficient in that approximately 80% of the transplanted islets die within a few days after infusion.

Furthermore, insulin independence is usually not sustainable in the long term, with typically less than half of the treated patients being insulin independent one year after the treatment.

Another disadvantage of the Edmonton Protocol is that multiple, preferably three, donor pancreata are needed for the treatment of one patient.

This contributes to the already existing lack organ donors.

Hence, until this day there is no therapy for diabetes type 1 available that provides a long-term control of the disease.

Although many treatment combinations may be theoretically thinkable, no combination treatment, in particular including immune suppressive agents, in the prior art yielded satisfactory results to date.

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